Overview

Overview:

The Collagen Antibody Induced Arthritis (CAIA) model is a relevant model for studying the efferent phase of RA, where leukocytes are attracted and respond to the immune complex in the joint. It is induced using a cocktail of antibodies to anti-CII and contains pathogenic features similar to that of RA such as pannus formation, cellular infiltration, synovitis and cartilage/bone destruction.

Benefits of the CAIA model

Length of study: Arthritis develops in mice typically within 24-48 hr allowing the completion of a study within 2 weeks reducing the number of assessments and scoring periods.

Reduced group size: Rate of incidence is nearly 100% depending on the strain allowing for smaller group sizes.

Susceptibility: Arthritis is induced not only in CIA-susceptible DBA/1 and B10.RIII mice, but also in some CIA-resistant mice, such as Balb/c.

Eliminates expensive colonies: Models such as the K/BxN serum transfer model require labs to maintain expensive colonies and the sera can vary from batch to batch.

Figure: Balb/c were administered 2 mg of ArthritoMab antibody cocktail on day 0 followed by a LPS boost on day 3. Unlike competitor products, disease progression is steady and controlled for easy evaluation of prophylactic and therapeutic regimes.

Comparison

ArthritoMab™

Competitor

Epitopes Recognized

CB11, CB10, CB8

CB11 only

Disease Progression

Steady & Controlled

Rapid & Severe

Paw involvement

Consistent & Predominantely rear

Variable & unpredictable

Animals/vial

25

20

Abreviations:

Anti-Collagen Induced arthritis (ACIA)

Monoclonal Antibody induced arthritis (mAb-RA)

Collagen Antibody Induced Arthritis (CAIA)

Data/Specifications

Data/Specifications:

Epitope specificity

The classic CIA model is mediated by autoantibodies which bind to type II collagen and complement. In mice as well as human RA patients, the antibody response that best correlates with disease is directed against the C1, J1 and U1 epitopes. The ArthritoMab™ arthritogenic cocktail of 4 monoclonal antibodies binds to these well-defined epitopes C11b, J1, D3 and U1, which are spread over the entire CII (CB8, CB10 and CB11 fragments). This possibly encourages better immune complex formation on the cartilage surface for the initiation of arthritis and produces consistent and predictable disease in all 4 paws (with predominance for the rear). Competitor products only recognize CB11, which produces variable disease that can contribute to unpredictable involvement in the paws (sometimes more front paw involvment and other times more rear involvement).

Susceptibility

Balb/c

DBA/1

B10.RIII

C57Bl/6

Disease Progression & Positive controls

Disease progression is steady and controlled using ArthritoMab™ antibody cocktail, enabling investigators to evaluate various regimes. Data below was generated using Vehicle, Dexamethasone and Enbrel in the Balb/c strain (induced with 2 mg ArthritoMab™ on day 0 followed by LPS boost on day 3).

Histopathology:

Histopathological changes in the joints are scored on a scale of 0-4 for seven different parameters. Histopathology in the balb/c induced with ArthritoMab™ antibody cocktail share similarities with the CIA model.The images below show histological joint changes on day 12 in Balb/c when induced with 2 mg ArthritoMab™ Antibody Cocktail. Synovial Hyperplasia (left), cellular infiltration (middle), cartilage & bone erosion (right).

Induce arthritis in 8- and 10-week old BALB/c mice. On day 0, mice were injected intraperitoneally with 4 mg of ArthritoMab. On day 3, mice were boosted intraperitoneally with 50 ug of lipopolysacharide in 200 ul sterile PBS.

Induce arthritis in BALB/c mice. On day 0, 100 mg/kg (2 mg/mouse) of ArithritoMab was injected to induce arthritis. At day 5 or 3 respectively, lipopolysacharide (LPS) was injected intraperitoneally (50 ug/mouse) to enhance the incidence.

Induce arthritis in genetically modified mice backcrossed to the arthritis-susceptible DBA/1 strain. Each mouse recieved a total of 4mg of ArthritoMab transferred intravenously in two consecutive days. On the fourth day, a 50ug boost of LPS was given by intraperitoneal injection.

For the Induction of Arthritis in the Collagen Antibody Induced Arthritis Model:

Administer antibody cocktail (IV) on day 0 with 2 mg*

Boost with LPS on day 3 (IP)

Body weights, clinical signs & scoring, rear paw thickness

Terminate on day 12

Histopathology

*Needs to be optimized for each laboratory. MD Biosciences contract research service runs the Collagen Antibody Induced Arthritis model using the ArthritoMab™ cocktail on a monthly basis. Scientists can assist in setting up the model in each lab, walking through optimizations not only based on your individual vivarium conditions, but also based on your compound requirements. We use a variety of administration routes and compound classes and can assist in recommending the best approach for your situation.